MRAP2 melanocortin 2 receptor accessory protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MRAP2provided by HGNC
Official Full Name: melanocortin 2 receptor accessory protein 2provided by HGNC
Primary source: HGNC:HGNC:21232
See related: Ensembl:ENSG00000135324 MIM:615410; AllianceGenome:HGNC:21232
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: C6orf117; bA51G5.2
Summary: This gene encodes a protein that modulates melanocortin receptor signaling. The encoded protein has been shown to interact with all known melanocortin receptors and may regulate both receptor trafficking and activation in response to ligands. Mice lacking a functional copy of this gene exhibit severe obesity and a mutation in this gene may be associated with severe obesity in human patients. [provided by RefSeq, Oct 2016]
Expression: Broad expression in brain (RPKM 4.0), adrenal (RPKM 2.1) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q14.2

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (84033178..84146282)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (85256469..85369574)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (84743491..84800600)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.
Title: Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.
Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2.
Title: Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2.
The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a.
Title: The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a.
The pleiotropic metabolic effect of loss-of-function mutations in MRAP2 might be due to the failure of different MRAP2-regulated G-protein-coupled receptors in various tissues including pancreatic islets.
Title: Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension.
Data found that MRAP2 was significantly up-regulated in women with unexplained infertility. The epithelium of the uterine glands showed hypertrophy in women with unexplained infertility. MRAP2 expression alteration in the endometrium on infertile women suggestes a potential role in regulating endometrial stability.
Title: MRAP2 regulates endometrial receptivity and function.
The accepted idea that melanocortin Receptor Accessory Proteins (MRAPs) are specific regulators of melanocortin receptors was recently challenged by the discovery that MRAP2 inhibits the activity of prokineticin receptors. Recent studies are starting to explain the role of the unusual structure of MRAPs and to illustrate the importance of MRAP2 for the maintenance of both energy and glucose homeostasis. [review]
Title: Melanocortin Receptor Accessory Proteins (MRAPs): Functions in the melanocortin system and beyond.
In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1. Importantly, like MC4R and PKRs, OX1R is predominately expressed in the brain where it regulates food intake
Title: Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling.
This was the first study describing an effect of a MRAP2 mutation on mediated by regulation of the melanocortin-4 receptor FUNCTION IN HUMAN.
Title: Decreased melanocortin-4 receptor function conferred by an infrequent variant at the human melanocortin receptor accessory protein 2 gene.
no gene harboring deletions were identified in the SIM1 and MRAP2 regions in the Prader Willi like (PWL) cohort; further functional analysis of p.P352S found in SIM1 and p.A40S found in MRAP2 is useful; this would provide further support for possible role of SIM1 and MRAP2 in the pathogenesis of the PWL phenotype in a limited number of patients
Title: Copy number variation (CNV) analysis and mutation analysis of the 6q14.1-6q16.3 genes SIM1 and MRAP2 in Prader Willi like patients.
Data show that co-expression with MRAPalpha, but not MRAP2, enhances MC4R constitutive activity. MRAPalpha-enhanced MC4R constitutive activity is not dependent on MC4R complex glycosylation but may result from MRAPalpha-induced changes in MC4R conformational states.
Title: hMRAPα, but Not hMRAP2, Enhances hMC4R Constitutive Activity in HEK293 Cells and This Is Not Dependent on hMRAPα Induced Changes in hMC4R Complex N-linked Glycosylation.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Body mass index quantitative trait locus 18 MedGen: C3714940 OMIM: 615457 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-AA039481 (e-PCR)
- UniSTS:74651

G59311 (e-PCR)
- UniSTS:136626

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables corticotropin hormone receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables corticotropin hormone receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables type 1 melanocortin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables type 1 melanocortin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables type 3 melanocortin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables type 3 melanocortin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables type 4 melanocortin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables type 4 melanocortin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables type 5 melanocortin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables type 5 melanocortin receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in energy homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in energy reserve metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in feeding behavior	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: melanocortin-2 receptor accessory protein 2

Names: MC2R accessory protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_051944.2 RefSeqGene

Range

5596..62705

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001346541.2 → NP_001333470.1 melanocortin-2 receptor accessory protein 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream translation start site compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.

Source sequence(s)

AK307078, BC010003, BU629097

UniProtKB/Swiss-Prot

Q96G30
NM_001346542.2 → NP_001333471.1 melanocortin-2 receptor accessory protein 2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 3 and 5 encode the same isoform (1).

Source sequence(s)

AL161621, BU629097

Consensus CDS

CCDS5001.1

UniProtKB/Swiss-Prot

A8K9M1, Q8IXM9, Q8N2D1, Q96G30

Conserved Domains (1) summary

pfam15183
Location:13 → 99

MRAP; Melanocortin-2 receptor accessory protein family
NM_001346543.2 → NP_001333472.1 melanocortin-2 receptor accessory protein 2 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and contains a novel 5' coding region compared to variant 1. The encoded isoform (3) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AL161621, BU629097
NM_001346544.2 → NP_001333473.1 melanocortin-2 receptor accessory protein 2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 3 and 5 encode the same isoform (1).

Source sequence(s)

AL161621, BU629097

Consensus CDS

CCDS5001.1

UniProtKB/Swiss-Prot

A8K9M1, Q8IXM9, Q8N2D1, Q96G30

Conserved Domains (1) summary

pfam15183
Location:13 → 99

MRAP; Melanocortin-2 receptor accessory protein family
NM_138409.4 → NP_612418.2 melanocortin-2 receptor accessory protein 2 isoform 1

See identical proteins and their annotated locations for NP_612418.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1, 3 and 5 encode the same isoform (1).

Source sequence(s)

BC010003

Consensus CDS

CCDS5001.1

UniProtKB/Swiss-Prot

A8K9M1, Q8IXM9, Q8N2D1, Q96G30

Related

ENSP00000257776.4, ENST00000257776.5

Conserved Domains (1) summary

pfam15183
Location:13 → 99

MRAP; Melanocortin-2 receptor accessory protein family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

84033178..84146282

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017010220.2 → XP_016865709.1 melanocortin-2 receptor accessory protein 2 isoform X2

UniProtKB/Swiss-Prot

A8K9M1, Q8IXM9, Q8N2D1, Q96G30

Conserved Domains (1) summary

pfam15183
Location:13 → 99

MRAP; Melanocortin-2 receptor accessory protein family
XM_017010221.3 → XP_016865710.1 melanocortin-2 receptor accessory protein 2 isoform X3

Conserved Domains (1) summary

pfam15183
Location:13 → 80

MRAP; Melanocortin-2 receptor accessory protein family
XM_047418132.1 → XP_047274088.1 melanocortin-2 receptor accessory protein 2 isoform X1
XM_047418133.1 → XP_047274089.1 melanocortin-2 receptor accessory protein 2 isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

85256469..85369574

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054354132.1 → XP_054210107.1 melanocortin-2 receptor accessory protein 2 isoform X2

UniProtKB/Swiss-Prot

A8K9M1, Q8IXM9, Q8N2D1, Q96G30
XM_054354133.1 → XP_054210108.1 melanocortin-2 receptor accessory protein 2 isoform X3
XM_054354131.1 → XP_054210106.1 melanocortin-2 receptor accessory protein 2 isoform X1
XM_054354134.1 → XP_054210109.1 melanocortin-2 receptor accessory protein 2 isoform X4